[ CAS No. 1224288-92-9 ] {[proInfo.proName]}

Name: 1224288-92-9|5-Chloropyrazolo[1,5-a]pyrimidine-3-carbonitrile|98%
Brand: Ambeed
SKU: A280775
Price: 11.0 USD
Availability: InStock
Rating: 92 (30 reviews)

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

DV 2D 3D

3d Animation Molecule Structure of 1224288-92-9

Structure of 1224288-92-9 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 1224288-92-9 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 1224288-92-9 ]

SDS Specification

Alternatived Products of [ 1224288-92-9 ]

Product Details of [ 1224288-92-9 ]

CAS No. :	1224288-92-9	MDL No. :	MFCD18073765
Formula :	C₇H₃ClN₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	OYGONYREIXSORZ-UHFFFAOYSA-N
M.W :	178.58	Pubchem ID :	71627118
Synonyms :

Calculated chemistry of [ 1224288-92-9 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	42.71
TPSA :	53.98 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.67 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.48
Log Po/w (XLOGP3) :	1.01
Log Po/w (WLOGP) :	1.25
Log Po/w (MLOGP) :	0.58
Log Po/w (SILICOS-IT) :	1.03
Consensus Log Po/w :	1.07

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-2.14
Solubility :	1.3 mg/ml ; 0.00727 mol/l
Class :	Soluble
Log S (Ali) :	-1.73
Solubility :	3.3 mg/ml ; 0.0185 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.41
Solubility :	0.69 mg/ml ; 0.00386 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.93

Safety of [ 1224288-92-9 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 1224288-92-9 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 1224288-92-9 ]
Downstream synthetic route of [ 1224288-92-9 ]

[ 1224288-92-9 ] Synthesis Path-Upstream 1~5

1
[ 1224288-95-2 ]
[ 1224288-92-9 ]

Yield	Reaction Conditions	Operation in experiment
53.8%	at 150℃; for 4 h;	A mixture of 5-hydroxypyrazolo[1,5-ajpyrimidine-3-carbonitrile (10.00 g, 62.45 mmol)PQC13 (200.00 mL) was heated to 150°C for 4 hrs. After TLC (PE:EtOAc = 1:1) showed thereaction was complete, the mixture was concentrated to remove POC13, then dissolved in DCMmL), concentrated and purified by column chromatography on silica gel (DCM) to give 5-chloropyrazolo [1 ,5-ajpyrimidine-3 -carbonitrile (6.00 g, yield: 53.80percent) as a white solid.

Reference： [1] Patent: WO2017/87778, 2017, A1, . Location in patent: Page/Page column 27; 28

2
[ 1224288-95-2 ]
[ 1224288-92-9 ]

Yield	Reaction Conditions	Operation in experiment
23%	at 150℃; for 3 h;	A mixture of 5-oxo-4,5-dihydropyrazolo[1,5-a]pyrimidine-3-carbonitrile (1.33 g, 8.31 mmol) and POCl₃ (7.74 mL, 83 mmol) was heated at 150° C. for 3 hours and cooled to room temperature. After concentration in vacuo, the residue was purified by column chromatography on SiO₂ (Hex:EtOAc=2:1) to afford 5-chloropyrazolo[1,5-a]pyrimidine-3-carbonitrile (343 mg, 23percent) as a white solid. ¹H-NMR (CDCl₃, Varian, 400 MHz): δ 7.09 (1H, d, J=7.6 Hz), 8.39 (1H, s), 8.68 (1H, d, J=7.2 Hz).

Reference： [1] Heterocycles, 2010, vol. 80, # 2, p. 1359 - 1376
[2] Patent: US2016/168156, 2016, A1, . Location in patent: Paragraph 0448; 0452; 0453

3
[ 1621718-74-8 ]
[ 1224288-92-9 ]

Yield	Reaction Conditions	Operation in experiment
42%	at 140℃; for 18 h;	A solution of (E)-5-chloropyrazolo[1,5-a]pyrimidine-3-carbaldehyde oxime (280 mg, 1.42 mmol) in Ac₂O (20 mL) was stirred at 140° C. for 18 hours, then cooled to rt and concentrated in vacuo. The residue was washed with Et₂O (20 mL) to give the title compound as a yellow solid (106 mg, 42percent). [0323] MS (ESI, pos. ion) m/z: 179.1 [M+H]⁺.

Reference： [1] Patent: US2014/234254, 2014, A1, . Location in patent: Paragraph 0322; 0323

4
[ 29274-24-6 ]
[ 1224288-92-9 ]

Reference： [1] Patent: US2014/234254, 2014, A1,

5
[ 1256162-94-3 ]
[ 1224288-92-9 ]

Reference： [1] Patent: US2014/234254, 2014, A1,

[ 1224288-92-9 ] Synthesis Path-Downstream 1~34

1
[ 1224288-92-9 ]
[ 1224288-99-6 ]
[ 478081-98-0 ]

Reference： [1]Heterocycles,2010,vol. 80,p. 1359 - 1376

2
[ 1224288-95-2 ]
[ 1224288-92-9 ]

Yield	Reaction Conditions	Operation in experiment
23%	With trichlorophosphate; at 150.0℃; for 3.0h;	A mixture of 5-oxo-4,5-dihydropyrazolo[1,5-a]pyrimidine-3-carbonitrile (1.33 g, 8.31 mmol) and POCl3 (7.74 mL, 83 mmol) was heated at 150 C. for 3 hours and cooled to room temperature. After concentration in vacuo, the residue was purified by column chromatography on SiO2 (Hex:EtOAc=2:1) to afford 5-chloropyrazolo[1,5-a]pyrimidine-3-carbonitrile (343 mg, 23%) as a white solid. 1H-NMR (CDCl3, Varian, 400 MHz): delta 7.09 (1H, d, J=7.6 Hz), 8.39 (1H, s), 8.68 (1H, d, J=7.2 Hz).

Reference： [1]Heterocycles,2010,vol. 80,p. 1359 - 1376
[2]Patent: US2016/168156,2016,A1 .Location in patent: Paragraph 0448; 0452; 0453

3
[ 1224288-92-9 ]
[ 30418-59-8 ]
[ 1224289-06-8 ]

Reference： [1]Heterocycles,2010,vol. 80,p. 1359 - 1376

4
[ 1224288-92-9 ]
[ 13331-27-6 ]
[ 1224289-04-6 ]

Reference： [1]Heterocycles,2010,vol. 80,p. 1359 - 1376

5
[ 1224288-92-9 ]
[ 78887-39-5 ]
[ 1224289-08-0 ]

Reference： [1]Heterocycles,2010,vol. 80,p. 1359 - 1376

6
[ 29274-24-6 ]
[ 1224288-92-9 ]

Reference： [1]Patent: US2014/234254,2014,A1

7
[ 1256162-94-3 ]
[ 1224288-92-9 ]

Reference： [1]Patent: US2014/234254,2014,A1

8
[ 1621718-74-8 ]
[ 1224288-92-9 ]

Yield	Reaction Conditions	Operation in experiment
42%	With acetic anhydride; at 140.0℃; for 18.0h;	A solution of (E)-5-chloropyrazolo[1,5-a]pyrimidine-3-carbaldehyde oxime (280 mg, 1.42 mmol) in Ac2O (20 mL) was stirred at 140 C. for 18 hours, then cooled to rt and concentrated in vacuo. The residue was washed with Et2O (20 mL) to give the title compound as a yellow solid (106 mg, 42%). [0323] MS (ESI, pos. ion) m/z: 179.1 [M+H]+.

Reference： [1]Patent: US2014/234254,2014,A1 .Location in patent: Paragraph 0322; 0323

9
[ 1083326-73-1 ]
[ 1224288-92-9 ]
[ 1621718-29-3 ]

Yield	Reaction Conditions	Operation in experiment
75.3%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,4-dioxane; water; at 90.0℃; for 5.0h;Inert atmosphere;	2,4-difluoro-N-(2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzenesulfonamide (383 mg, 0.9 mmol), <strong>[1224288-92-9]5-chloropyrazolo[1,5-a]pyrimidine-3-carbonitrile</strong> (106 mg, 0.6 mmol), Pd(dppf)Cl2.CH2Cl2 (49 mg, 0.06 mmol) and Na2CO3 (254 mg, 2.5 mmol) were placed into a two-neck flask, then degassed with N2 for 3 times, and followed by adding 1,4-dioxane (12 mL) and water (2 mL). The mixture was degassed with N2 for 3 times again, then heated to 90 C. and stirred further for 5 hours. The mixture was cooled to rt, and filtered. The filtrate was concentrated in vacuo and the residue was purified by a silica gel column chromatography (PE/EtOAc (v/v)=4/3) to give the title compound as a light yellow solid (200 mg, 75.3%). [0325] HPLC: 97%; MS (ESI, pos. ion) m/z: 443.2 [M+H]+; 1H NMR (400 MHz, DMSO-d6) delta (ppm): 10.51 (s, 1H), 9.41 (d, J=7.4 Hz, 1H), 8.93 (d, J=2.1 Hz, 1H), 8.81 (s, 1H), 8.45 (d, J=2.2 Hz, 1H), 7.99 (d, J=7.5 Hz, 1H), 7.85-7.78 (m, 1H), 7.61-7.52 (m, 1H), 7.25 (t, J=8.4 Hz, 1H), 3.77 (s, 3H).

Reference： [1]Patent: US2014/234254,2014,A1 .Location in patent: Paragraph 0324; 0325; 0326; 0327

10
[ 886503-15-7 ]
[ 1224288-92-9 ]
5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	In dimethyl sulfoxide; at 180.0℃; for 1.0h;	A mixture of <strong>[1224288-92-9]5-chloropyrazolo[1,5-a]pyrimidine-3-carbonitrile</strong> (343 mg, 1.92 mmol) and 2-(2,5-difluorophenyl)pyrrolidine (Intermediate 2, 343 mg, 1.87 mmol) in DMSO (10 mL) was heated at 180 C. for 1 hour and cooled to room temperature. The reaction mixture was diluted with water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (Hex:EtOAc=2:1 to 1:1) to afford 5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (611 mg, 98%) as a ivory solid. 1H-NMR (CDCl3, Varian, 400 MHz): delta 2.05-2.11 (3H, m), 2.47-2.55 (1H, m), 3.67-4.10 (2H, m), 5.20 (0.7H, s), 5.65 (0.3H, s), 5.96 (0.7H, s), 6.43 (0.3H, s), 6.69-6.73 (1H, m), 6.96-7.09 (2H, m), 8.01-8.31 (3H, m).

Reference： [1]Patent: US2016/168156,2016,A1 .Location in patent: Paragraph 0448; 0454; 0455

11
[ 1224288-92-9 ]
5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide [ No CAS ]

Reference： [1]Patent: US2016/168156,2016,A1

12
[ 1224288-92-9 ]
(Z)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)-N-(1-(dimethylamino)ethylidene)pyrazolo[1,5-a]pyrimidine-3-carboxamide [ No CAS ]

Reference： [1]Patent: US2016/168156,2016,A1

13
[ 1224288-92-9 ]
5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3-(5-methyl-1H-1,2,4-triazol-3-yl)pyrazolo[1,5-a]pyrimidine [ No CAS ]

Reference： [1]Patent: US2016/168156,2016,A1

14
[ 1224288-92-9 ]
5-((2R,4S)-4-fluoro-2-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile [ No CAS ]

Reference： [1]Patent: WO2017/87778,2017,A1

15
[ 1224288-92-9 ]
5-((2R,4S)-4-fluoro-2-(5-fluoro-1-methyl-2-oxo-1,2-dihydropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile [ No CAS ]

Reference： [1]Patent: WO2017/87778,2017,A1

16
[ 1224288-92-9 ]
3-((2R,4S)-1-(3-cyanopyrazolo[1,5-a]pyrimidin-5-yl)-4-fluoropyrrolidin-2-yl)-5-fluorobenzoic acid [ No CAS ]

Reference： [1]Patent: WO2017/87778,2017,A1

17
[ 1224288-92-9 ]
3-((2R,4S)-1-(3-cyanopyrazolo[1,5-a]pyrimidin-5-yl)-4-fluoropyrrolidin-2-yl)-5-fluoro-N-methylbenzamide [ No CAS ]

Reference： [1]Patent: WO2017/87778,2017,A1

18
[ 1224288-92-9 ]
methyl 2-((2R,4S)-1-(3-cyanopyrazolo[1,5-a]pyrimidin-5-yl)-4-fluoropyrrolidin-2-yl)-4-fluorobenzoate [ No CAS ]

Reference： [1]Patent: WO2017/87778,2017,A1

19
[ 1224288-92-9 ]
2-((2R,4S)-1-(3-cyanopyrazolo[1,5-a]pyrimidin-5-yl)-4-fluoropyrrolidin-2-yl)-4-fluorobenzoic acid [ No CAS ]

Reference： [1]Patent: WO2017/87778,2017,A1

20
[ 1224288-92-9 ]
2-((2R,4S)-1-(3-cyanopyrazo[1,5-a]pyrimidin-5-yl)-4-fluoropyrrolidin-2-yl)-4-fluorobenzamide [ No CAS ]

Reference： [1]Patent: WO2017/87778,2017,A1

21
[ 1224288-92-9 ]
3-fluoro-5-((2R,4S)-4-fluoropyrrolidin-2-yl)pyridine dihydrochloride [ No CAS ]
5-((2R,4S)-4-fluoro-2-(5-fluoropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58.63%	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 130.0℃; for 16.0h;	To a mixture of 5-chioropyrazolo [1 ,5-ajpyrimidine-3 -carbonitrile (86.00 mg, 334.49 umol, 1.20 eq) and 3-fluoro-5-((2R,4S)-4-fluoropyrrolidin-2-yl)pyridine HC1 (49.78 mg, 278.74 umol,1.00 eq) in dioxane (6.00 mL) was added DIPEA (108.07 mg, 836.23 umol, 3.00 eq) in one portion.The mixture was stirred at 130C for 16 hrs. LCMS showed the reaction was complete. The reaction mixture was purified by acidic prep-HPLC to afford 5-((2R,4S)-4-fluoro-2-(5- fluoropyridin-3 -yl)pyrrolidin- 1 -yl)pyrazolo [1 ,5-ajpyrimidine-3 -carbonitrile (90.60 mg, 163.43 umol, yield: 58.63%) as a yellow oil.

Reference： [1]Patent: WO2017/87778,2017,A1 .Location in patent: Page/Page column 27; 29

22
[ 1224288-92-9 ]
3-[(2R)-4,4-difluoropyrrolidin-2-yl]-5-fluoro-pyridine [ No CAS ]
(R)-5-(4,4-difluoro-2-(5-fluoropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%	With N-ethyl-N,N-diisopropylamine; In butan-1-ol; at 100.0℃; for 16.0h;	To a mixture of 5-chloropyrazolo[1,5-ajpyrimidine-3-carbonitrile (40.00 mg, 223.99 umol, 1.00 eq) and 3- [(2R)-4,4-difluoropyrrolidin-2-ylj -5-fluoro-pyridine (61.62 mg, 223.99 umol, 1.00eq) in n-BuOH (2.00 mL) was added DIPEA (144.74 mg, 1.12 mmol, 5.00 eq). The resulting mixture was stirred at 100C for 16 hrs. The mixture was concentrated and the crude product was purified by acidic prep-HPLC (TFA system). (R)-5-(4,4-difluoro-2-(5-fluoropyridin-3 - yl)pyrrolidin- 1 -yl)pyrazolo [1 ,5-ajpyrimidine-3 -carbonitrile (48.70 mg, 85.09 umol, yield: 38%) was obtained as a brown solid.

Reference： [1]Patent: WO2017/87778,2017,A1 .Location in patent: Page/Page column 29

23
[ 1224288-92-9 ]
[ 1364890-34-5 ]
5-((2R,4S)-2-(3-cyano-5-fluorophenyl)-4-fluoropyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
10.2%	With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In 1,4-dioxane; at 110.0℃; for 4.0h;	5-Chioropyrazolo [1 ,5-ajpyrimidine-3 -carbonitrile (0.075 g, 0.420 mmol), 3 -fluoro-5-((2R,4S)-4-fluoropyrrolidin-2-yl)benzonitrile (0.096 g, 0.462 mmol) and Cs2CO3 (0.411 g, 1.260 mmol) were taken up in dioxane (2 ml). Pd2(dba)3 (0.038 g, 0.042 mmol) and BINAP (0.052 g, 0.084 mmol) were added and stirred at 110 C for 4 hours. The solvent was removed in vacuo. The residue was purified via reverse phase chromatography (0-100% ACN/H20) to give 5-((2R,4S)-2- (3-cyano-5-fluorophenyl)-4-fluoropyrrolidin- 1 -yl)pyrazolo [1 ,5-ajpyrimidine-3 -carbonitrile (0.015g, 0.043 mmol, 10.20 % yield) as a white foam.

Reference： [1]Patent: WO2017/87778,2017,A1 .Location in patent: Page/Page column 33

24
[ 1224288-92-9 ]
(3S,5R)-5-(2,5-difluorophenyl)pyrrolidine-3-carbonitrile [ No CAS ]
5-((2R,4S)-4-cyano-2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
10.81%	With N-ethyl-N,N-diisopropylamine; In butan-1-ol; at 100.0℃; for 16.0h;	To a mixture of 5-chloropyrazolo [1 ,5-ajpyrimidine-3 -carbonitrile (50.00 mg, 279.99 umol,) in n-BuOH (3.00 mL) was added DIPEA (72.37 mg, 559.98 umol) and (3S,5R)-5-(2,5-difluorophenyl)pyrrolidine-3-carbonitrile (58.30 mg, 279.99 umol). The mixture was stirred at100C for 16 hrs. LCMS showed the reaction was complete. The reaction mixture was concentrated to give the crude product. The crude product was purified by neutral prep-HPLC to give 5-((2R,4S )-4-cyano-2-(2,5-difluorophenyl)pyrrolidin- 1 -yl)pyrazolo [1 ,5-ajpyrimidine-3 - carbonitrile (10.60 mg, 30.26 umol, yield: 10.8 1%) as a white solid.

Reference： [1]Patent: WO2017/87778,2017,A1 .Location in patent: Page/Page column 32

25
[ 1224288-92-9 ]
5-fluoro-3-((2R,4S)-4-fluoropyrrolidin-2-yl)-2-methoxypyridine hydrochloride [ No CAS ]
5-((2R,4S)-4-fluoro-2-(5-fluoro-2-methoxypyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With N-ethyl-N,N-diisopropylamine; In butan-1-ol; at 110.0℃; for 1.0h;Microwave irradiation;	A mixture of 5-chloropyrazolo[1,5-ajpyrimidine-3-carbonitrile (88.5 mg, 0.50 mmol), 5-fluoro-3 -((2R,4S )-4-fluoropyrrolidin-2-yl)-2-methoxypyridine hydrochloride (124 mg, 0.50 mmol)and DIEA (0.26 mL, 1.50 mmol) in n-butanol (2.5 mL) was heated in a microwave reactor at 110Cfor 60 minutes. The mixture was concentrated to remove solvents and the residue was purified bycolumn chromatography on silica gel to give 5-((2R,4S)-4-fluoro-2-(5-fluoro-2-methoxypyridin-3- yl)pyrrolidin- 1 -yl)pyrazolo [1 ,5-ajpyrimidine-3 -carbonitrile as a white solid (168 mg, yield: 95%).

Reference： [1]Patent: WO2017/87778,2017,A1 .Location in patent: Page/Page column 33; 34

26
[ 1224288-92-9 ]
1-(3-fluoro-5-((2R,4S)-4-fluoropyrrolidin-2-yl)phenyl)ethan-1-one [ No CAS ]
5-((2R,4S)-2-(3-acetyl-5-fluorophenyl)-4-fluoropyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60.77%	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 100.0℃; for 2.0h;	To a mixture of 5-chloropyrazolo[1,5-ajpyrimidine-3-carbonitrile (80.00 mg, 447.98 umol,1.00 eq) in dioxane (5.00 mL) was added DIPEA (173.69 mg, 1.34 mmol, 234.72 uL, 3.00 eq) and1 -(3-fluoro-5-((2R,45)-4-fluoropyrrolidin-2-yl)phenyl)ethan- 1-one (99.89 mg, 443.50 umol, 0.99eq). The mixture was stirred at 100C for 2 hrs. LCMS showed the reaction was complete. The mixture was concentrated to give the crude product. The crude product was purified by prep -TLC (PE:EtOAc = 1:1) to give 5-((2R,4S)-2-(3-acetyl-5-fluorophenyl)- 4-fluoropyrrolidin- 1- yl)pyrazolo[1,5-ajpyrimidine-3-carbonitrile (100.00 mg, 272.22 umol, yield: 60.77%) as a yellowoil.

Reference： [1]Patent: WO2017/87778,2017,A1 .Location in patent: Page/Page column 36; 37

27
[ 1224288-92-9 ]
1-(3-fluoro-5-((2R,4S)-4-fluoropyrrolidin-2-yl)phenyl)ethan-1-one [ No CAS ]
5-((2R,4S)-4-fluoro-2-(3-fluoro-5-(2-hydroxypropan-2-yl)phenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile [ No CAS ]

Reference： [1]Patent: WO2017/87778,2017,A1

28
[ 1224288-92-9 ]
methyl 3-fluoro-5-((2R,4S)-4-fluoropyrrolidin-2-yl)benzoate [ No CAS ]
methyl 3-((2R,4S)-1-(3-cyanopyrazolo[1,5-a]pyrimidin-5-yl)-4-fluoropyrrolidin-2-yl)-5-fluorobenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
650 mg	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 100.0℃; for 16.0h;	To a mixture of methyl 3-fluoro-5-((2R,4S)-4-fluoropyrrolidin-2-yl)benzoate (400.00 mg, 2.24 mmol, 1.00 eq) in dioxane (50.00 mL) was added DIPEA (868.45 mg, 6.72 mmol, 3.00 eq) and5-chloropyrazolo [1 ,5-ajpyrimidine-3 -carbonitrile (540.00 mg, 2.24 mmol, 1.00 eq). The mixturewas stirred at 100C for 16 hrs. The mixture was concentrated to give the crude product. The crude product was purified by column chromatography on silica gel (PE:EtOAc = 10:1-3:1) to give methyl 3-((2R,4S)- 1 -(3-cyanopyrazolo[ 1 ,5-ajpyrimidin-5-yl)- 4-fluoropyrrolidin-2-yl)-5- fluorobenzoate (650.00 mg, 1.70 mmol, yield: 75.89%) as a yellow oil. ?H-NMR (400 MHz, CD3OD) 5 ppm 8.30-8.24 (m, 1H), 6.94-6.83 (m, 2H), 5.64 (t, 1H, J = 9.2 Hz), 5.41 (d, 1H, J = 52.0Hz), 4.48-4.3 8 (m, 2H), 3.97 (s, 3H), 2.79-2.69 (m, 1H), 2.20-2.06 (m, 1H).

Reference： [1]Patent: WO2017/87778,2017,A1 .Location in patent: Page/Page column 39

29
[ 1224288-92-9 ]
(2R,45)-2-(2-bromo-5-fluoro-phenyl)-4-fluoro-pyrrolidine [ No CAS ]
5-((2R,4S)-2-(2-bromo-5-fluorophenyl)-4-fluoropyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; water; at 80.0℃; for 16.0h;	A mixture of 5-chloropyrazolo[1,5-ajpyrimidine-3-carbonitrile (500.00 mg, 2.33 mmol, 1.00 eq, HC1), (2R,45)-2-(2-bromo-5-fluoro-phenyl)-4-fluoro-pyrrolidine (694.17 mg, 2.33 mmol, 1.00 eq, HC1), DIPEA (751.26 mg, 5.81 mmol, 1.02 mL, 2.50 eq) in dioxane (8.00 mL) was stirredat 80C for 16 hrs. TLC (PE:EtOAc = 3:1) showed the reaction was complete. To the mixture wasadded H20 (10 mL), and then the mixture was extracted with EtOAc (10 mL * 3). The combined organic layers were dried over Na2SO4, concentrated in vacuum to get 5-((2R,4S)-2-(2-bromo-5- fluorophenyl)-4-fluoropyrrolidin- 1 -yl)pyrazolo [1 ,5-ajpyrimidine-3 -carbonitrile (1.00 g, crude) as a yellow oil.

Reference： [1]Patent: WO2017/87778,2017,A1 .Location in patent: Page/Page column 40; 41

30
[ 1224288-95-2 ]
[ 1224288-92-9 ]

Yield	Reaction Conditions	Operation in experiment
53.8%	With trichlorophosphate; at 150.0℃; for 4.0h;	A mixture of 5-hydroxypyrazolo[1,5-ajpyrimidine-3-carbonitrile (10.00 g, 62.45 mmol)PQC13 (200.00 mL) was heated to 150C for 4 hrs. After TLC (PE:EtOAc = 1:1) showed thereaction was complete, the mixture was concentrated to remove POC13, then dissolved in DCMmL), concentrated and purified by column chromatography on silica gel (DCM) to give 5-chloropyrazolo [1 ,5-ajpyrimidine-3 -carbonitrile (6.00 g, yield: 53.80%) as a white solid.

Reference： [1]Patent: WO2017/87778,2017,A1 .Location in patent: Page/Page column 27; 28

31
[ 1224288-92-9 ]
(R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)-N-hydroxypyrazolo[1,5-a]pyrimidine-3-carboximidamide [ No CAS ]

Reference： [1]Patent: WO2020/114499,2020,A1

32
[ 1224288-92-9 ]
(R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboximidamide [ No CAS ]

Reference： [1]Patent: WO2020/114499,2020,A1

33
[ 1224288-92-9 ]
(R)-2-(5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3,4,6,7-tetrahydropyrano[3,4-d]imidazole [ No CAS ]

Reference： [1]Patent: WO2020/114499,2020,A1

34
[ 1218935-60-4 ]
[ 1224288-92-9 ]
[ 1260846-28-3 ]

Yield	Reaction Conditions	Operation in experiment
92%	With N-ethyl-N,N-diisopropylamine; In ethanol; at 90.0℃; for 2.0h;	To a solution of ethyl 5-chloropyrazolo [1, 5-a] pyrimidine-3-carbonitrile (17.8 g) in EtOH (400 mL) was added (R) -2- (2, 5-difluorophenyl) pyrrolidine hydrochloride (26.2 g) and DIEA (25.8 g) . The mixture was heated to 90 for 2 h. [0621] TLC showed the reaction was completed, Concentrated under reduced pressure to remove EtOH and the residue was poured into cooled water and filtered, the solid was washed with 1N HCl and water, dried under reduce pressure at 60 for 10h to afford the desired product (R) -5- (2- (2, 5-difluorophenyl) pyrrolidin-1-yl) pyrazolo [1, 5-a] pyrimidine-3-carbonitrile (29.9 g, 92%) as a white solid.

Reference： [1]Patent: WO2020/114499,2020,A1 .Location in patent: Page/Page column 81

Same Skeleton Products

Related Products

Historical Records

Related Functional Groups of
[ 1224288-92-9 ]

Chlorides

[ 845895-95-6 ]

5,7-Dichloropyrazolo[1,5-a]pyrimidine-3-carbonitrile

Similarity: 0.85

[ 29274-24-6 ]

5-Chloropyrazolo[1,5-a]pyrimidine

Similarity: 0.84

[ 189116-36-7 ]

5-Chloro-2-methylpyrazolo[1,5-a]pyrimidine

Similarity: 0.80

[ 779353-64-9 ]

5,7-Dichloro-3-ethylpyrazolo[1,5-a]pyrimidine

Similarity: 0.74

[ 960613-96-1 ]

3-Bromo-5-chloropyrazolo[1,5-a]pyrimidine

Similarity: 0.73

Nitriles

[ 845895-95-6 ]

5,7-Dichloropyrazolo[1,5-a]pyrimidine-3-carbonitrile

Similarity: 0.85

[ 51516-67-7 ]

5-Amino-1-(4-chlorophenyl)-1H-pyrazole-4-carbonitrile

Similarity: 0.61

[ 51516-68-8 ]

5-Amino-1-(3-chlorophenyl)-1H-pyrazole-4-carbonitrile

Similarity: 0.60

[ 158001-28-6 ]

5-Amino-1-(tert-butyl)-1H-pyrazole-4-carbonitrile

Similarity: 0.58

[ 5334-43-0 ]

5-Amino-1-phenyl-1H-pyrazole-4-carbonitrile

Similarity: 0.58

Related Parent Nucleus of
[ 1224288-92-9 ]

Other Aromatic Heterocycles

[ 845895-95-6 ]

5,7-Dichloropyrazolo[1,5-a]pyrimidine-3-carbonitrile

Similarity: 0.85

[ 29274-24-6 ]

5-Chloropyrazolo[1,5-a]pyrimidine

Similarity: 0.84

[ 189116-36-7 ]

5-Chloro-2-methylpyrazolo[1,5-a]pyrimidine

Similarity: 0.80

[ 779353-64-9 ]

5,7-Dichloro-3-ethylpyrazolo[1,5-a]pyrimidine

Similarity: 0.74

[ 960613-96-1 ]

3-Bromo-5-chloropyrazolo[1,5-a]pyrimidine

Similarity: 0.73

Ghs Precautionary Statements

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 1224288-92-9 ] {[proInfo.proName]}

Quality Control of [ 1224288-92-9 ]

Related Doc. of [ 1224288-92-9 ]

Product Details of [ 1224288-92-9 ]

Calculated chemistry of [ 1224288-92-9 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 1224288-92-9 ]

Application In Synthesis of [ 1224288-92-9 ]

[ 1224288-92-9 ] Synthesis Path-Upstream 1~5

[ 1224288-92-9 ] Synthesis Path-Downstream 1~34

Related Functional Groups of [ 1224288-92-9 ]

Chlorides

Nitriles

Related Parent Nucleus of [ 1224288-92-9 ]

Other Aromatic Heterocycles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 1224288-92-9 ]

Related Parent Nucleus of
[ 1224288-92-9 ]